Abstract
Objective: To investigate the expression of p16, cyclin D1 and Rb protein in gastric carcinoma and premalignant lesions including dysplastic gastric mucosa and intestinal metaplasia gastric mucosa. Methods: Using SP immunohistochemical methods, the expression of p16, cyclin D1 and Rb proteins was detected in 10 specimens of normal gastric mucosa, 15 specimens of dysplastic gastric mucosa, 15 specimens of intestinal metaplasia gastric mucosa, 30 specimens of gastric carcinoma. The clinical characteristics of the 30 patients with gastric carcinoma were analysed to explore the relationship between the parameter detected and biological action of gastric cancer. Results: Expression of p16 protein was detected in 90% of normal gastric mucosa, 86.67% of dysplastic gastric mucosa, 86.67% of intestinal metaplasia gastric mucosa, 36.67% of gastric carcinoma. The positive rate of p16 protein expression in gastric carcinoma is significantly lower than that in normal gastric mucosa and gastric premalignant lesions mucosa (P<0.01). Expression of cyclin D1 protein was detected in 10% of normal gastric mucosa, 20% of dysplastic gastric mucosa, 20% of intestinal metaplasia gastric mucosa, 53.33% of gastric carcinoma. The positive rate of cyclin D1, protein expression in gastric carcinoma is significantly higher than that in normal gastric mucosa and gastric premalignant lesions mucosa (P<0.05). Expression of Rb protein was detected in 90% of normal gastric mucosa, 80% of dysplastic gastric mucosa, 80% of intestinal metaplasia gastric mucosa, 50% of gastric carcinoma. The positive rate of Rb protein expression in gastric carcinoma is significantly lower than that in normal gastric mucosa (P<0.05). The expression of p16, cyclin D1 gene were associated with the degree of differentiation of gastric carcinoma, lymphnodes metastasis and distant metastasis. Conclusion: p16, Cyclin D1 and Rb gene play important role in gastric carcinoma genesis. The expression of p16, cyclin D1 and Rb gene have some value to the diagnosis at earlier stage of gastric cancer. Detection of expression of p16, cyclin D1 gene would be helpful to judge the prognosis of gastric cancer.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Serrano M, Hannon GJ, Beach D. A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4 [J]. Nature 1993; 366:704.
Lang JC, Tobin EJ, Knobloch TJ, et al. Frequent mutation of p16 in squamous cell carcinoma of the head and neck [J]. Laryngoscope 1998; 108:923.
Hashemi J, Platz A, Ueno T, et al. CDKN2A germ-line mutations in individuals with multiple cutaneous melanomas [J]. Cancer Res 2000; 60:6864.
Faderl S, Kantarjian HM, Estey E, et al. The prognostic significance of p16 (INK4a)/p14 (ARF) locus deletion and MDM-2 protein expression in adult acute myelogenous leukemia [J]. Cancer 2000; 89:1976.
Cachia AR, Indsto JO, McLaren KM, et al. CDKN2A mutation and deletion status in thin and thick primary melanoma [J]. Clin Cancer Res 2000; 6:3511.
Mochizuki S, Iwadate Y, Namba H, et al. Homozygous deletion of the p16/MTS-1/CDKN2 gene in malignant gliomas is infrequent among Japanese patients [J]. Int J Oncol 1999; 15:983.
Nakamura M, Sugita K, Inukai T, et al. p16/MTS1/INK4A gene is frequently inactivated by hyper-methylation in childhood acute lymphoblastic leukemia with 11q23 translocation [J]. Leukemia 1999; 13:884.
Orlow I, Drobnjak M, Zhang ZF. Alterations of INK4A and INK4B genes in adult soft tissue sarcomas: effect on survival [J]. J Natl Cancer Inst 1999; 91:73.
Borg A, Sandberg T, Nilsson K, et al. High frequency of multiple melanomas and breast and pancreas carcinomas in CDKN2A mutation positive melanoma families [J]. J Natl Cancer Inst 2000; 92:1260.
Monzon J, Liu L, Brill H, et al. CDKN2A mutations in multiple primary melanomas [J]. N Engl J Med 1998; 338:879.
Oue N, Motoshita J, Yokozaki H, et al. Distinct promoter hypermethylation of p16 INK4a, CDH1, and RAR-beta in intestinal, diffuse-adherent, and diffuse-scattered type gastric carcinomas [J]. J Pathol 2002; 198:55.
Lee TL, Leung WK, Chan MW, et al. Detection of gene promoter hypermethylation in the tumor and serum of patients with gastric carcinoma [J]. Clin Cancer Res 2002; 8:1761.
Leung WK, Yu J, Ng EK, et al. Concurrent hypermethylation of multiple tumor-related genes in gastric carcinoma and adjacent normal tissues [J]. Cancer 2001; 91:2294.
Aoyagi K, Koufuji K, Yano S, et al. Immunohistochemical study on the expression of cyclin D1 and E in gastric cancer [J]. Kurume Med J 2000; 47:199.
Chen YT, Shih LS, Chen YM. Quantitative analysis of CDKN2, p53 and retinoblastoma mRNA in human gastric carcinoma [J]. Int J Oncol 1998; 13:249.
Zhang Yin-chang. Gastric mucosa biopsy. In: China National Cancer Research and Control Office & China Anti-Cancer Association, eds. Common Malignant Tumor Normative Standard of Diagnosis and Treatment in China [M]. Beijing: Beijing Medical University & China Union Medical University Publishing Company. 1990; 36.
Wang TB, Gao P, Qu YG, et al. Expression and significance of p15 and p16 gene in human gastric carcinoma (in Chinese) [J]. Chin J Clin Oncol Rehabil 2001; 8:23.
Sarbia M, Stahl M, Fink U, et al. Prognostic significance of cyclin D1 in esophageal squamous cell carcinoma patients treated with surgery alone or combined therapy modalities [J]. Int J Cancer 1999; 84:86.
Author information
Authors and Affiliations
Corresponding author
Additional information
Biography: MIAO Lin (1966–), male, master of medicine, associate professor, Second Affiliated Hospital, Nanjing Medical University, majors in gastroenterological cancer.
Rights and permissions
About this article
Cite this article
Miao, L., Zhao, Zq., Ji, Gz. et al. Expression of p16, cyclin D1 and RB protein in gastric carcinoma and premalignant lesions. Chin. J. Cancer Res. 15, 58–62 (2003). https://doi.org/10.1007/s11670-003-0013-3
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s11670-003-0013-3